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Publication : Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.

First Author  Amador-Noguez D Year  2005
Journal  Biochem Biophys Res Commun Volume  332
Issue  4 Pages  1086-100
PubMed ID  15925325 Mgi Jnum  J:99117
Mgi Id  MGI:3581314 Doi  10.1016/j.bbrc.2005.05.063
Citation  Amador-Noguez D, et al. (2005) Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice. (Correction to gene names in Table 4 appears in BBRC 2005;334:733-35). Biochem Biophys Res Commun 332(4):1086-100
abstractText  Genetic mutations that increase lifespan in mice frequently involve alterations in the growth hormone/insulin-like growth factor-I signaling pathway. Although several of the effects of GH on gene expression are known to be sex-dependent, an understanding of the gender-specific vs. gender-independent effects of lifespan-extending mutations of the GH/IGF-I axis is currently lacking. The Ames dwarf mice (prop1(df/df)) are GH, prolactin and thyroid-stimulating hormone deficient and exhibit an increase in mean lifespan of 49% in males and 68% in females. We used oligonucleotide arrays containing over 14,000 genes to study the gender-specific vs. gender-independent effects of the prop1(df) mutation in liver of male and female Ames mice. We identified 381 gender-independent and 110 gender-specific alterations in gene expression produced by the Prop1(df/df) genotype. The gender-specific alterations corresponded to genes with a strong sexual dimorphism in wild-type mice and produced an almost complete loss of sex-specific gene expression in the liver of Ames dwarf mice: out of 123 genes that showed sexual dimorphism in wild-type mice only six maintained a gender difference in mutant mice. However, the Prop1(df/df) genotype did not introduce new sexually dimorphic patterns of gene expression in Ames dwarf mice that were not present in the wild-type animals. The gender-specific alterations accounted for a large fraction of the most significant changes in gene expression in male and female Ames mice livers and affected several metabolic processes, particularly fatty acid metabolism, steroid hormone metabolism, and xenobiotic metabolism.
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